Regarding metal/drug interaction experiments, previous self-administration reports have been limited to the effects of adult lead or cadmium exposure on ethanol or cocaine intake. To date, there have been no studies on the effects of developmental metal exposure on the patterns of drug selection and intake later in the adult cycle. Relevant to this issue, this laboratory has observed that responsiveness to cocaine and other dopamine agonists is altered by perinatal exposure to lead or cadmium, and these disturbances persist well into the adult cycle long after toxicants have gained clearance from soft tissue. Such seemingly permanent and potentially nonreversible effects are of potential importance with respect to predicting use patterns of drugs that impact dopamine and related systems. Accordingly, this project aims to investigate the effects of prenatal, postnatal, and perinatal exposure to lead or cadmium on the self-administration of cocaine, heroin, and combinations of heroin and cocaine. Dams will be exposed to 0, 8, or 16 mg lead (Exp. 1-3) or 0, 2.5, or 5 mg cadmium (Exp. 4-6), and cross-fostered pups will be tested as adults for the intravascular (iv) self-administration of cocaine, heroin, or cocaine/heroin combinations (speedball). Exp. 7-9 will determine the effects of prenatal, postnatal, and perinatal cadmium exposure on regional accumulation of cadmium in brain, as well as in blood, liver, kidney, and bone (tibia). Because lead exists in such high concentrations in the inner cities where drug abuse is more common, and because over 20 percent of pregnant women in the United States smoke tobacco that contains cadmium which is readily distributed to the fetus/neonate, results of the proposed project should enhance our understanding of possible linkages between environmental contamination during early development and drug selection and use later in life.